Background: The DNA binding domain of HMG proteins is known to be important in many diseases, with the Sox\r\nsub-family of HMG proteins of particular significance. Numerous natural variants in HMG proteins are associated\r\nwith disease phenotypes. Integrating these natural variants, molecular dynamic simulations of DNA interaction and\r\nsequence and structure alignments give detailed molecular knowledge of potential amino acid function such as\r\nDNA or protein interaction.\r\nResults: A total of 33 amino acids in HMG proteins are known to have natural variants in diseases. Eight of these\r\namino acids are normally conserved in human HMG proteins and 27 are conserved in the human Sox sub-family.\r\nAmong the six non-Sox conserved amino acids, amino acids 16 and 45 are likely targets for interaction with other\r\nproteins. Docking studies between the androgen receptor and Sry/Sox9 reveals a stable amino acid specific\r\ninteraction involving several Sox conserved residues.\r\nConclusion: The HMG box has structural conservation between the first two of the three helixes in the domain as\r\nwell as some DNA contact points. Individual sub-groups of the HMG family have specificity in the location of the\r\nthird helix, DNA specific contact points (such as amino acids 4 and 29), and conserved amino acids interacting\r\nwith other proteins such as androgen receptor. Studies such as this help to distinguish individual members of a\r\nmuch larger family of proteins and can be applied to any protein family of interest.
Loading....